Non-cAMP-mediated bronchial arterial vasodilation in response to inhaled beta-agonists.
We studied the dose-dependent effects of inhaled isoetharine HCl, a beta-adrenergic bronchodilator (2.5, 5.0, 10.0, and 20.0 mg), on bronchial blood flow (Qbr) in anesthetized sheep. Isoetharine resulted in a dose-dependent increase in Qbr. With a total dose of 17.5 mg, Qbr increased from baseline values of 22 +/- 3.4 (SE) to 60 +/- 16 ml/min (P < 0.001), an effect independent of changes in cardiac output and systemic arterial pressure. To further study whether synthesis of endogenous nitric oxide (NO) affects beta-agonist-induced increases in Qbr, we administered isoetharine (20 mg) by inhalation before and after the NO-synthase inhibitor N omega-nitro-L-arginine methyl ester (L-NAME). Intravenous L-NAME (30 mg/kg) rapidly decreased Qbr by approximately 80% of baseline, whereas L-NAME via inhalation (10 mg/kg) resulted in a delayed and smaller (approximately 22%) decrease. Pretreatment with L-NAME via both routes of administration attenuated bronchial arterial vasodilation after subsequent challenge with isoetharine. We conclude that isoetharine via inhalation increases Qbr in a dose-dependent manner and that beta-agonist-induced relaxation of vascular smooth muscle in the bronchial vasculature is partially mediated via synthesis of NO.
Carvalho
P
P
Pulmonary Research Laboratory, Department of Veterans Affairs Medical Center, Boise, Idaho 83702, USA.
Johnson
S R
SR
Charan
N B
NB
D000280:Administration, Inhalation; D000316:Adrenergic alpha-Agonists / Q000494:pharmacology; D000318:Adrenergic beta-Agonists / Q000008:administration & dosage / Q000494:pharmacology*; D000818:Animals; D001981:Bronchial Arteries / Q000187:drug effects*; D000242:Cyclic AMP / Q000502:physiology*; D004305:Dose-Response Relationship, Drug; D004791:Enzyme Inhibitors / Q000008:administration & dosage / Q000494:pharmacology; D006439:Hemodynamics / Q000187:drug effects; D007275:Injections, Intravenous; D007528:Isoetharine / Q000008:administration & dosage / Q000494:pharmacology; D019331:NG-Nitroarginine Methyl Ester / Q000008:administration & dosage / Q000494:pharmacology; D019001:Nitric Oxide Synthase / Q000037:antagonists & inhibitors; D010101:Oxygen Consumption / Q000187:drug effects; D010656:Phenylephrine / Q000494:pharmacology; D012756:Sheep; D014664:Vasodilation / Q000187:drug effects*
D000316:Adrenergic alpha-Agonists; D000318:Adrenergic beta-Agonists; D004791:Enzyme Inhibitors; D010656:Phenylephrine; D000242:Cyclic AMP; D019001:Nitric Oxide Synthase; D019331:NG-Nitroarginine Methyl Ester; D007528:Isoetharine